Labetalol HCl

MOLECULAR FORMULA :

C19-H24-N2-O3.Cl-H

MOLECULAR WEIGHT :

364.91

WISWESSER LINE NOTATION :

ZVR BQ EYQ1MY1&2R &GH

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

244 mg/kg/76D-I

TOXIC EFFECTS :

Liver - liver function tests impaired Lungs, Thorax, or Respiration - other changes

REFERENCE :

AJMEAZ American Journal of Medicine. (Technical Pub., 875 Third Ave., New York, NY 10022) V.1- 1946- Volume(issue)/page/year: 87,235,1989

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

360 mg/kg/60D-I

TOXIC EFFECTS :

Liver - jaundice (or hyperbilirubinemia) hepatocellular Liver - liver function tests impaired

REFERENCE :

AIMEAS Annals of Internal Medicine. (American College of Physicians, 4200 Pine St., Philadelphia, PA 19104) V.1- 1927- Volume(issue)/page/year: 113,210,1990

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

1620 mg/kg/27W-I

TOXIC EFFECTS :

Gastrointestinal - other changes Liver - jaundice (or hyperbilirubinemia) hepatocellular Kidney, Ureter, Bladder - other changes in urine composition

REFERENCE :

AIMEAS Annals of Internal Medicine. (American College of Physicians, 4200 Pine St., Philadelphia, PA 19104) V.1- 1927- Volume(issue)/page/year: 113,210,1990

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

53 mg/kg/53D-I

TOXIC EFFECTS :

Liver - jaundice (or hyperbilirubinemia) hepatocellular Skin and Appendages - dermatitis, other (after systemic exposure)

REFERENCE :

AIMEAS Annals of Internal Medicine. (American College of Physicians, 4200 Pine St., Philadelphia, PA 19104) V.1- 1927- Volume(issue)/page/year: 113,210,1990

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

2114 mg/kg

TOXIC EFFECTS :

Behavioral - altered sleep time (including change in righting reflex) Behavioral - convulsions or effect on seizure threshold Nutritional and Gross Metabolic - body temperature decrease

REFERENCE :

KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 21,6307,1987

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

107 mg/kg

TOXIC EFFECTS :

Behavioral - convulsions or effect on seizure threshold

REFERENCE :

HOIZAK Hokkaido Igaku Zasshi. Hokkaido Journal of Medical Science. (Hokkaido Daigaku Igakubu, Nishi-7-chome, Kita-15-jo, Kita-ku, Sapporo, Japan) V.1- 1923- Volume(issue)/page/year: 53,15,1978

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

53 mg/kg

TOXIC EFFECTS :

Behavioral - convulsions or effect on seizure threshold

REFERENCE :

HOIZAK Hokkaido Igaku Zasshi. Hokkaido Journal of Medical Science. (Hokkaido Daigaku Igakubu, Nishi-7-chome, Kita-15-jo, Kita-ku, Sapporo, Japan) V.1- 1923- Volume(issue)/page/year: 53,15,1978

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

1450 mg/kg

TOXIC EFFECTS :

Behavioral - somnolence (general depressed activity) Behavioral - convulsions or effect on seizure threshold

REFERENCE :

HOIZAK Hokkaido Igaku Zasshi. Hokkaido Journal of Medical Science. (Hokkaido Daigaku Igakubu, Nishi-7-chome, Kita-15-jo, Kita-ku, Sapporo, Japan) V.1- 1923- Volume(issue)/page/year: 53,15,1978

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

114 mg/kg

TOXIC EFFECTS :

Behavioral - convulsions or effect on seizure threshold

REFERENCE :

HOIZAK Hokkaido Igaku Zasshi. Hokkaido Journal of Medical Science. (Hokkaido Daigaku Igakubu, Nishi-7-chome, Kita-15-jo, Kita-ku, Sapporo, Japan) V.1- 1923- Volume(issue)/page/year: 53,15,1978

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

47 mg/kg

TOXIC EFFECTS :

Behavioral - convulsions or effect on seizure threshold

REFERENCE :

HOIZAK Hokkaido Igaku Zasshi. Hokkaido Journal of Medical Science. (Hokkaido Daigaku Igakubu, Nishi-7-chome, Kita-15-jo, Kita-ku, Sapporo, Japan) V.1- 1923- Volume(issue)/page/year: 53,15,1978

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

>1500 mg/kg

TOXIC EFFECTS :

Behavioral - tremor Behavioral - ataxia Gastrointestinal - nausea or vomiting

REFERENCE :

JZKEDZ Jitchuken Zenrinsho Kenkyuho. Central Institute for Experimental Animals, Research Reports. (Jikken Dobutsu Chuo Kenkyusho, 1433 Nogawa, Takatsu-ku, Kawasaki 211, Japan) V.1- 1975- Volume(issue)/page/year: 6,273,1980

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rabbit

DOSE/DURATION :

1250 mg/kg

TOXIC EFFECTS :

Behavioral - convulsions or effect on seizure threshold

REFERENCE :

HOIZAK Hokkaido Igaku Zasshi. Hokkaido Journal of Medical Science. (Hokkaido Daigaku Igakubu, Nishi-7-chome, Kita-15-jo, Kita-ku, Sapporo, Japan) V.1- 1923- Volume(issue)/page/year: 53,15,1978

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - rabbit

DOSE/DURATION :

41 mg/kg

TOXIC EFFECTS :

Behavioral - convulsions or effect on seizure threshold Behavioral - ataxia

REFERENCE :

HOIZAK Hokkaido Igaku Zasshi. Hokkaido Journal of Medical Science. (Hokkaido Daigaku Igakubu, Nishi-7-chome, Kita-15-jo, Kita-ku, Sapporo, Japan) V.1- 1923- Volume(issue)/page/year: 53,15,1978 ** OTHER MULTIPLE DOSE TOXICITY DATA **

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

13500 mg/kg/30D-I

TOXIC EFFECTS :

Liver - changes in liver weight Kidney, Ureter, Bladder - changes in bladder weight Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol)

REFERENCE :

JTSCDR Journal of Toxicological Sciences. (Japanese Soc. of Toxicological Sciences, 4th Floor, Gakkai Center Bldg., 4-16, Yayoi 2-chome, Bunkyo-ku, Tokyo 113, Japan) V.1- 1976- Volume(issue)/page/year: 5,353,1980

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

27300 mg/kg/39W-I

TOXIC EFFECTS :

Cardiac - changes in heart weight Kidney, Ureter, Bladder - other changes in urine composition Nutritional and Gross Metabolic - changes in potassium

REFERENCE :

JTSCDR Journal of Toxicological Sciences. (Japanese Soc. of Toxicological Sciences, 4th Floor, Gakkai Center Bldg., 4-16, Yayoi 2-chome, Bunkyo-ku, Tokyo 113, Japan) V.1- 1976- Volume(issue)/page/year: 6,37,1981

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

21600 mg/kg/13W-I

TOXIC EFFECTS :

Liver - changes in liver weight Kidney, Ureter, Bladder - urine volume increased Blood - changes in leukocyte (WBC) count

REFERENCE :

KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 21,6314,1987

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

2730 mg/kg/13W-I

TOXIC EFFECTS :

Gastrointestinal - changes in structure or function of salivary glands Gastrointestinal - hypermotility, diarrhea Gastrointestinal - nausea or vomiting

REFERENCE :

JZKEDZ Jitchuken Zenrinsho Kenkyuho. Central Institute for Experimental Animals, Research Reports. (Jikken Dobutsu Chuo Kenkyusho, 1433 Nogawa, Takatsu-ku, Kawasaki 211, Japan) V.1- 1975- Volume(issue)/page/year: 6,273,1980 ** REPRODUCTIVE DATA **

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

DOSE :

600 ug/kg

SEX/DURATION :

female 35 week(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - cardiovascular (circulatory) system Reproductive - Specific Developmental Abnormalities - respiratory system Reproductive - Effects on Newborn - Apgar score (human only)

REFERENCE :

AJPEEK American Journal of Perinatology. (Thieme Medical Publishers, Inc. 381 Park Ave. S., New York, NY 10157-0208) V.1- 1983- Volume(issue)/page/year: 11,91,1994

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

3150 mg/kg

SEX/DURATION :

male 63 day(s) pre-mating

TOXIC EFFECTS :

Reproductive - Paternal Effects - testes, epididymis, sperm duct Reproductive - Fertility - mating performance (e.g. # sperm positive females per # females mated; # copulations per # estrus cycles)

REFERENCE :

YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 9,839,1981

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

1 gm/kg

SEX/DURATION :

female 17-22 day(s) after conception lactating female 14 day(s) post-birth

TOXIC EFFECTS :

Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain)

REFERENCE :

YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 9,879,1981

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

3850 mg/kg

SEX/DURATION :

female 7-17 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Embryo or Fetus - extra-embryonic structures (e.g., placenta, umbilical cord) Reproductive - Effects on Embryo or Fetus - fetal death

REFERENCE :

YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 9,851,1981

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

1650 mg/kg

SEX/DURATION :

female 7-17 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus)

REFERENCE :

YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 9,851,1981

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

550 mg/kg

SEX/DURATION :

female 7-17 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - musculoskeletal system

REFERENCE :

YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 9,851,1981

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

1800 mg/kg

SEX/DURATION :

female 17-22 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Newborn - stillbirth

REFERENCE :

YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 9,879,1981

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

100 mg/kg

SEX/DURATION :

female 7-16 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Newborn - other neonatal measures or effects Reproductive - Effects on Newborn - biochemical and metabolic

REFERENCE :

AIPBE4 Archives Internationalos de Physiologie, de Biochimie et de Biophysique. (Vaillant-Carmanne, s.a., Zeven Puttenstraat 20, 3690 Zutendaal, Belgium) V.99- 1991- Volume(issue)/page/year: 100,355,1992

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

650 mg/kg

SEX/DURATION :

female 6-18 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - musculoskeletal system

REFERENCE :

YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 9,869,1981 *** REVIEWS *** TOXICOLOGY REVIEW PBPSDY Pharmacological and Biochemical Properties of Drug Substances. (American Pharmaceutical Assoc., 2215 Constitution Ave., NW, Washington, DC 20037) V.1- 1977- Volume(issue)/page/year: 2,229,1979